Schistosoma mansoni: Influence of immunization and challenge schedules on the sites and mechanisms of resistance in CBA/Ca mice vaccinated with highly irradiated cercariae

ABSTRACTThese studies address current controversies over the site(s) of challenge attrition in the murine irradiated vaccine model of immunity toSchistosoma mansoni. Two possibilities have been investigated. Firstly, that the site of death of the radiation-attenuated schistosomes used to vaccinate the mice may vary in different laboratories and secondly, that the skin sites selected for presentation of the immunizing and challenge parasites may influence the final site at which immunity is effected (i.e. ear/abdomen vs tail/tail). The migration of radiolabelled cercariae exposed to 0, 20 or 50 krad of gamma irradiation from the NIMR60Cobalt source was examined in CBA/Ca mice by squashed organ autoradiography. Unirradiated parasites all migrated from the skin to the lungs, and 65% moved on to the liver. Migration of parasites attenuated by exposure to 20 krad of gamma irradiation was delayed, but 76% finally reached the lungs; only 1% was recruited to the liver. The majority of 50 krad attenuated parasites died in the skin, with only 4% accomplishing migration to the pulmonary vasculature. The major site of death (and by implication of antigenic stimulation) of the 20 krad attenuated NIMR strainS. mansoniused routinely for vaccination purposes in our laboratory, is thus the lungs, a finding that does not explain the fact that immunity is mediated primarily in the skin in our model system. Site elimination experiments and squashed organ autoradiography showed conclusively that, irrespective of the skin sites chosen for presentation of the immunizing and challenge population of worms, NIMR challenge parasites are killed predominantly in the skin of vaccinated CBA/Ca mice. Moreover, qualitative and quantitative histological examination of the challenged tail skin of vaccinated mice revealed that inflammatory reactions comprising mononuclear cells and eosinophils develop in this site and function to trap and eliminate challenge larvae, despite a reported reduction in antigen presenting cells in this region.

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Schistosoma mansoni: evidence that ‘non-permissiveness’ in 129/Ola mice involves worm relocation and attrition in the lungs

Parasitology ◽

10.1017/s0031182000059084 ◽

1989 ◽

Vol 99 (3) ◽

pp. 365-375 ◽

Cited By ~ 11

Author(s):

A. A. F. Elsaghier ◽

P. M. Knopf ◽

G. F. Mitchell ◽

D. J. Mclaren

Keyword(s):

Schistosoma Mansoni ◽

Primary Infection ◽

Histological Analysis ◽

Liver Parenchyma ◽

Pulmonary Vasculature ◽

Inflammatory Reactions ◽

Recovery Techniques ◽

Worm Recovery ◽

Worm Migration ◽

Kinetics Of

Summary129/Ola mice resemble WEHI 129J mice in that around 70% of the individuals in any given population resist a primary infection withSchistosoma mansoni. Squashed-organ autoradiographic tracking of [Se]selenomethionine-labelled parasites has shown that the kinetics of worm migration in 129/Ola mice follows the expected pattern, and that all rodents harbour essentially similar numbers of worms on day 14 post-infection. Combined lung and liver worm recovery techniques have revealed, however, that segregation of mice into ‘permissive’ and ‘non-permissive’ individuals can first be detected on day 20. ‘Non-permissive’ mice are characterized by the absence of schistosome eggs at all times in the liver parenchyma and, in consequence, lack the attendant manifestations of pathology; they do, however, harbour a few stunted worms in the liver and significant numbers of adult schistosomes in the pulmonary vasculature. Histological analysis of sectioned lung tissue from such animals indicates that some lung-located schistosomes feed, pair and lay eggs. Nevertheless, eosinophil-enriched inflammatory reactions develop around such worms and the parasites themselves exhibit various manifestations of trauma, ranging from minor vacuolation to gut herniation and extrusion. The phenomenon of ‘non-permissiveness’ thus involves retardation of worm development in the liver and, in consequence, relocation of the parasites to the lungs, where they become subject to host effector responses.

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Dual interactions between alpha 2-adrenoceptor agonists and the proximal Na(+)-H+ exchanger

AJP Renal Physiology ◽

10.1152/ajprenal.1990.258.3.f636 ◽

1990 ◽

Vol 258 (3) ◽

pp. F636-F642 ◽

Cited By ~ 4

Author(s):

F. A. Gesek ◽

J. W. Strandhoy

Keyword(s):

Pertussis Toxin ◽

Structure And Function ◽

Adrenergic Agonists ◽

Major Site ◽

Alpha Adrenoceptor ◽

Kinase C ◽

Adrenoceptor Agonists ◽

22Na Uptake ◽

And Function ◽

Stimulation Of

In the kidney, the proximal nephron is a major site for Na+ reabsorption and H+ secretion. An electroneutral exchanger mediates the uptake of luminal Na+ with the secretion of cellular H+. In these studies, alpha-adrenoceptor-stimulated influx of 22Na+ into rat proximal tubules through the Na(+)-H+ exchanger was examined. The activity of this exchanger was defined as the component of 22Na+ uptake sensitive to inhibition by ethylisopropyl amiloride (EIPA) and was observed to be increased by both alpha 1- and alpha 2-adrenoceptor agonists as well as by phorbol 12-myristate 13-acetate (PMA). Selective alpha 2-adrenoceptor agonists produced a range of stimulation of EIPA-suppressible 22Na+ uptake: from a 72% increase above control with guanabenz to a 253% increase with B-HT 933. Because heterogeneity of alpha 2-adrenoceptor structure and function has been postulated, we examined whether the effects of alpha 2-adrenoceptors were sensitive to pertussis toxin. the responses to alpha 1-adrenoceptor agonists and PMA were unaffected, but the stimulation of Na(+)-H+ exchange by each of the selective alpha 2-adrenoceptor agonists tested was blocked. When Na(+)-H+ exchange was increased directly by PMA acting on protein kinase C, guanabenz but not B-HT 933 inhibited the response. The results indicated that the alpha 2-adrenoceptor agonists stimulated 22Na+ influx by activating a pertussis toxin-sensitive pathway but that certain alpha 2-adrenergic agonists such as guanabenz could additionally inhibit the exchanger through a pertussis toxin-resistant mechanism. This inhibition by guanabenz could be reversed by selective alpha 2-adrenoceptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

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Impact of transfection with total RNA of K562 cells upon antigen presenting, maturation, and function of human dendritic cells from peripheral blood mononuclear cells

Transfusion ◽

10.1111/j.1537-2995.2007.01098.x ◽

2007 ◽

Vol 47 (2) ◽

pp. 256-265 ◽

Cited By ~ 2

Author(s):

Li Gao ◽

Hua-hua Fan ◽

Hua-zhong Lu ◽

Xiao-xuan Nie ◽

Yan Liu ◽

...

Keyword(s):

Dendritic Cells ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

K562 Cells ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

And Function ◽

Human Dendritic Cells ◽

Antigen Presenting

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Dexamethasone Promotes Fungal Infection By Inhibition of APC Activation with Beta-Glucans Via STAT-3 and NF-κb

Blood ◽

10.1182/blood.v128.22.3710.3710 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3710-3710 ◽

Cited By ~ 1

Author(s):

Peter Brossart ◽

Philipp Kotthoff

Keyword(s):

Transcription Factors ◽

T Cell ◽

Cell Activation ◽

Tnf Alpha ◽

Cytokines And Chemokines ◽

Stat3 Signaling ◽

Beta Glucans ◽

And Function ◽

Antigen Presenting ◽

Stimulation Of

Abstract Treatment of patients with glucocorticoids can result in an increased risk of infection with pathogens such as fungi. Dectin-1 is a member of the C-type lectin receptor superfamily and was shown to be one of the major receptors for fungal beta-glucans. Activation of Dectin-1 increases the production of cytokines and chemokines and T-cell stimulatory capacity of DC and mediates resolution of fungal infections. Here we show that antigen-presenting cells generated in the presence of dexamethasone (Dex-DC) have a reduced capacity to stimulate T-cell proliferation and decreased expression of costimulatory molecules, that can not be enhanced upon stimulation with Dectin-1 ligands. Stimulation of Dex-DC with beta-glucans induced a strong upregulation of Syk phosphorylation and increased secretion of IL-10, while the production of IL-12, IL-23 and TNF-alpha was reduced. Downstream of Syk stimulation of Dectin-1 on Dex-DC resulted in phosphorylation of STAT3 and reduced nuclear localization of transcription factors involved in DC activation and function. Defects in the Dectin-1 molecule can result at least in increased mucosal infections with fungi in affected individuals. In our study we analyzed Dectin-1 expression and signaling in Dex-DC and compared it to immature dendritic cells (iDC). First, we analyzed whether DC that were generated in the presence of dexamethason (Dex-DC) express Dectin-1 on their surface. Dectin-1 was highly expressed on Dex-DC cells compared to iDC. Stimulation of iDC with zymosan or curdlan increased the expression of the maturation markers CD80, CD83 and CD86. In contrast, Dex-DC show a reduced upregulation of these markers. CD11b was expressed at lower levels on Dex-DC as compared to iDC and was downregulated on both subsets after stimulation with beta-glucans. CD11b is part of CR3, which was found to be another beta-glucan and collaborating receptor of Dectin-1. As exprected, dexamethasone-treatment of DC results in reduced capacity to stimulate the proliferation of allogeneic T-cells in a MLR- assay, that could not be increased by stimulation with Dectin-1 ligand curdlan or the TLR-4 ligand LPS. DC generated in the presence of dexamethasone secreted lower amounts of TNF-alpha, IL-23 and IL-12p70 upon stimulation with Curdlan. Interestingly, secretion of IL-10 was increased by Dex-DC. Secretion of cytokines by Dex-DC was Syk-dependent as shown by incubation of cells with the syk-inhibitor R406 prior to Dectin-1 stimulation with curdlan. Incubation of Dex-DC with beta-glucans resulted in increased phosphorylation of Syk as compared to iDC and strongly increased generation of superoxide-anions. Downstream of Syk, we observed a highly increased activation of STAT3 signaling while the induction of STAT3 signaling was absent in iDC. STAT3 mediates immune inhibitory effects on DC function by promoting expression and secretion of anti-inflammatory cytokines like IL-10 and subsequent inhibition of Th1- and Th17-mediated response. In nuclei of Dex-DC transcription factors which are important for dendritic cell activation and cytokine secretion were not detected. In contrast, p50 was found to accumulate in nuclei of Dex-DC which might contribute to IL-10 expression. The phosphatase SHP-1, which is thought to regulate Syk-activitiy, was found to be expressed at lower levels in Dex-DC. CD45, another Syk-regulating phosphatase was expressed at similar levels as compared to iDC. Dexamethasone inhibited the function and differentiation of monocyte derived DC and abrogated the immunological effects induced by interaction of fungal beta-glucans with Dectin-1. It inhibited the secretion of cytokines and chemokines by antigen-presenting cells such as TNF-alpha, IL-12 and IL-23, which are important for T-cell activation and reduced the upregulation of costimulatory molecules on the cell surface upon interaction with beta-glucans. This is probably due to a diminished nuclear expression of several transcription factors involved in DC differentiation and function. Furthermore, dexamethasone increased the expression of Dectin-1 and Syk-phosphorylation but redirected downstream signaling towards STAT-3 that results in production of IL-10, that further contributes to the inhibition of anti-fungal immune responses. Finally the phosphatase SHP-1 was expressed at lower levels in Dex-DC and might further be affected by Dectin-1 mediated oxidative stress. Disclosures No relevant conflicts of interest to declare.

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Inhibition of antigen-presenting cell function and stimulation of human peripheral blood mononuclear cells to express an antiinflammatory cytokine profile by the stress protein BiP: Relevance to the treatment of inflammatory arthritis

Arthritis & Rheumatism ◽

10.1002/art.20134 ◽

2004 ◽

Vol 50 (4) ◽

pp. 1164-1171 ◽

Cited By ~ 69

Author(s):

Valerie M. Corrigall ◽

Mark D. Bodman-Smith ◽

Melanie Brunst ◽

Hannah Cornell ◽

Gabriel S. Panayi

Keyword(s):

Inflammatory Arthritis ◽

Mononuclear Cells ◽

Cell Function ◽

Human Peripheral Blood ◽

Stress Protein ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Antigen Presenting ◽

Antiinflammatory Cytokine ◽

Stimulation Of

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Stimulation of production of prostaglandin E in gingival cells exposed to products of human blood mononuclear cells

Biochemical Journal ◽

10.1042/bj1980391 ◽

1981 ◽

Vol 198 (2) ◽

pp. 391-396 ◽

Cited By ~ 16

Author(s):

S M D'Souza ◽

D J Englis ◽

A Clark ◽

R G Russell

Keyword(s):

Mononuclear Cell ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Gingival Tissue ◽

Prostaglandin E ◽

Dependent Manner ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Gingival Cells ◽

Stimulation Of

1. Supernatant media from cultures of unstimulated human peripheral blood mononuclear cells contained one or more factors that increased by several hundred-fold the production of prostaglandin E by fibroblast-like cells derived from both inflamed and normal human gingival tissue. 2. This stimulation occurred in a dose-dependent manner and was completely inhibited by 14 microM-indomethacin. 3. Responsiveness to the factor declined as the age of the cell culture increased. 4. An increase in prostaglandin E production was first observed after a 2h exposure to the mononuclear cell factor(s) and could be prevented by cycloheximide. 5. Brief exposure (0.5 and 1.0 h) to mononuclear cell factor did not increase prostaglandin E production by the cells in a subsequent 72 h incubation in the absence of mononuclear cell factor. 6. Addition of arachidonate (10 microM and 15 microM) further enhanced stimulation of prostaglandin E production in response to mononuclear cell factor. 7. The stimulatory activity was resistant to digestion by trypsin, but was heat-labile, so that only 17% remained after treatment at 56 degrees C for 30 min.

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CERI, CEFX, and CPI: Largely Improved Positive Controls for Testing Antigen-Specific T Cell Function in PBMC Compared to CEF

Cells ◽

10.3390/cells10020248 ◽

2021 ◽

Vol 10 (2) ◽

pp. 248

Author(s):

Alexander A. Lehmann ◽

Pedro A. Reche ◽

Ting Zhang ◽

Maneewan Suwansaard ◽

Paul V. Lehmann

Keyword(s):

T Cell ◽

Mononuclear Cells ◽

Cell Function ◽

Racial Bias ◽

Immune Monitoring ◽

Functional Fitness ◽

Peripheral Blood Mononuclear ◽

Cell Immunity ◽

Antigen Presenting ◽

Positive Controls

Monitoring antigen-specific T cell immunity relies on functional tests that require T cells and antigen presenting cells to be uncompromised. Drawing of blood, its storage and shipment from the clinical site to the test laboratory, and the subsequent isolation, cryopreservation and thawing of peripheral blood mononuclear cells (PBMCs) before the actual test is performed can introduce numerous variables that may jeopardize the results. Therefore, no T cell test is valid without assessing the functional fitness of the PBMC being utilized. This can only be accomplished through the inclusion of positive controls that actually evaluate the performance of the antigen-specific T cell and antigen presenting cell (APC) compartments. For Caucasians, CEF peptides have been commonly used to this extent. Moreover, CEF peptides only measure CD8 cell functionality. We introduce here universal CD8+ T cell positive controls without any racial bias, as well as positive controls for the CD4+ T cell and APC compartments. In summary, we offer new tools and strategies for the assessment of PBMC functional fitness required for reliable T cell immune monitoring.

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Lipoxygenase Inhibition by Plant Extracts

Biomolecules ◽

10.3390/biom11020152 ◽

2021 ◽

Vol 11 (2) ◽

pp. 152

Author(s):

Melita Lončarić ◽

Ivica Strelec ◽

Tihomir Moslavac ◽

Drago Šubarić ◽

Valentina Pavić ◽

...

Keyword(s):

Fatty Acids ◽

Unsaturated Fatty Acids ◽

Inflammatory Reactions ◽

Long Term Storage ◽

Food Properties ◽

Lipoxygenase Inhibition ◽

Plant Families ◽

Term Storage ◽

Stimulation Of

Lipoxygenases are widespread enzymes that catalyze oxidation of polyunsaturated fatty acids (linoleic, linolenic, and arachidonic acid) to produce hydroperoxides. Lipoxygenase reactions can be desirable, but also lipoxygenases can react in undesirable ways. Most of the products of lipoxygenase reactions are aromatic compounds that can affect food properties, especially during long-term storage. Lipoxygenase action on unsaturated fatty acids could result in off-flavor/off-odor development, causing food spoilage. In addition, lipoxygenases are present in the human body and play an important role in stimulation of inflammatory reactions. Inflammation is linked to many diseases, such as cancer, stroke, and cardiovascular and neurodegenerative diseases. This review summarized recent research on plant families and species that can inhibit lipoxygenase activity.

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Phenotypic and Functional Alterations of Immune Effectors in Periodontitis; A Multifactorial and Complex Oral Disease

Journal of Clinical Medicine ◽

10.3390/jcm10040875 ◽

2021 ◽

Vol 10 (4) ◽

pp. 875

Author(s):

Kawaljit Kaur ◽

Shahram Vaziri ◽

Marcela Romero-Reyes ◽

Avina Paranjpe ◽

Anahid Jewett

Keyword(s):

Periodontal Disease ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Oral Disease ◽

Healthy Controls ◽

Healthy Individuals ◽

Tnf Α ◽

Blood Mononuclear Cells ◽

Ifn Γ ◽

And Function

Survival and function of immune subsets in the oral blood, peripheral blood and gingival tissues of patients with periodontal disease and healthy controls were assessed. NK and CD8 + T cells within the oral blood mononuclear cells (OBMCs) expressed significantly higher levels of CD69 in patients with periodontal disease compared to those from healthy controls. Similarly, TNF-α release was higher from oral blood of patients with periodontal disease when compared to healthy controls. Increased activation induced cell death of peripheral blood mononuclear cells (PBMCs) but not OBMCs from patients with periodontal disease was observed when compared to those from healthy individuals. Unlike those from healthy individuals, OBMC-derived supernatants from periodontitis patients exhibited decreased ability to induce secretion of IFN-γ by allogeneic healthy PBMCs treated with IL-2, while they triggered significant levels of TNF-α, IL-1β and IL-6 by untreated PBMCs. Interaction of PBMCs, or NK cells with intact or NFκB knock down oral epithelial cells in the presence of a periodontal pathogen, F. nucleatum, significantly induced a number of pro-inflammatory cytokines including IFN-γ. These studies indicated that the relative numbers of immune subsets obtained from peripheral blood may not represent the composition of the immune cells in the oral environment, and that orally-derived immune effectors may differ in survival and function from those of peripheral blood.

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